- Email: [email protected]
The Floppy Mitral Valve
138
home visits as against 2-4 in those without (P=0’03 and 0-004, respectively). Whilst this is not as rewarding a result as one might have hoped for, it is no cause for abandoning the concept, and at the end of the trial 90% of those recording their own B.P. regarded the method as useful. No-one has studied the benefits to patients, employers, and doctors in time or money. In view of the numbers, these are likely to be substantial to all parties. FINNERTY and othersl2 in one hypertension clinic found that the time spent waiting and the lack of personal relationship with the doctor were two potent reasons for defaulting. Visits to the doctor will still, of course, be necessary; and if fewer, there might be time to make them more personal. Once in a while, the aneroid sphygmomanometer should be checked against a mercury column; extra time will have to be spent also in explaining how to use the equipment, and under the N.H.S. there is the knotty problem of who is to pay for it. So long as self-recording does not worry and upset the patient or his family, the sense of responsibility engendered seems a worthwhile end in itself. This would not be the first instance of patients being entrusted with their own treatment, with medical back-up. This sort of doctor/patient relationship has existed for many years in the management of diabetes, where self-care is now being further developed with machines for measuring blood-sugar at home-a technique which seems to be popular with patients14 15 and a great help to their doctors. With blood-pressure we need to know more about the long-term results with self-recording, and, just because we are failing so often to lower patients’ B.P. adequately and commerce is hot on the trail, there is no justification for a sudden rush into this activity. Tradition inhibits doctors from crediting laymen with the ability to look after themselves. But there are strong arguments for putting the hypertensive ball into the patient’s court.
The
Floppy Mitral Valve
How are whoops, honks, clicks, and other systolic sounds connected? The answer is in the prolapsing-mitral-valve syndrome, which occurs when the mitral-valve leaflets balloon or prolapse into the left atrium during systole. The many names given to this syndrome-the floppy mitral valve, the ballooning mitral valve, the redundant-cusp syndrome, the systolic click-murmur syndrome, and so onl-reflect a shortage of agreement on what exactly the syndrome is. Until the early 1960s, sys13. Johnson, A. L., Taylor, D. W., Sackett, D. L., Dunnett, C. W., Shimizu, A. G. Can med. Ass. J. 1978, 119, 1034. 14. Sönksen, P. H., Judd, S. L., Lowy, C. Lancet, 1978, i,729. 15. Walford, S., Gale, E. A. M., Allison, S. P., Tattersall, R. B. ibid. p. 732. 1 Abrams, J. Am. Heart. J. 1976, 92, 413.
tolic clicks
were regarded as extracardiac. Then REID2 challenged this view; and subsequently BARLOW3 and others4 showed that both clicks and the "innocent" late systolic murmur heard at the apex can originate from the mitral valve. Thus the concept of the "mitral valve click-murmur syndrome" developed. Certain manoeuvres that diminish ventricular volume, such as amyl-nitrite inhalation, upright posture, and the strain phase of the Valsalva manoeuvre, may reduce the intensity of the murmur and move the click nearer the first heart-sound; whereas the reverse may occur with increased ventricular volume, for example with phenylephrine, squatting, and the release phase of the Valsalva manaeuvre.5 At the bedside, systolic sounds can sometimes be elucidated by listening with the patient in turn sitting, standing, and squatting.5 Alteration in heart-rate may cause the murmur and click to disappear altogether.6 These clicks and murmurs, angiography reveals, coincide with the point of maximal prolapse of the mitral valve into the left atrium.7 The mitral-valve abnormality varies from prolapse of single leaflets and lengthening of the chordae tendinese to gross mitral incompetence with ballooning of both leaflets. Clicks seem to occur in the milder abnormalities ; with slightly more severe disruption a late systolic murmur is heard; and with haemodynamically important mitral regurgitation the murmur is pansystolic.8 Real-time echocardiography clarifies matters further,9 10 three distinctive patterns being recognised-midsystolic buckling of one or both mitral-valve leaflets; pansystolic bowing; and pansystolic collapse. Pansystolic bowing is the most
frequent. 11I How
common
are
these
auscultatory, angio-
and echocardiographic findings? Systolic clicks or late systolic murmurs were found in 74 (6.3%) of 1169 healthy young females, of whom 60 also had positive echocardiographic findings. 12 Much the same incidence of mitral-valve prolapse was found in patients having routine angiography, this abnormality being unsuspected in just under half.13 Higher incidences have been reported, both
graphic,
2. 3.
Reid, J. V.O.S.Afr. med. J. 1961, 35, 353. Barlow, J. B., Bosman, C. K., Pocock, W. A., Marchand, P. Br. Heart J. 1968, 30, 203. 4. Hancock, E. W., Cohn, K. Am. J. Med. 1966, 41, 183. 5. Devereux, R. B., Perloff, J. K., Reichek, N., Josephson, M. E. Circulation, 1976, 54, 3. 6. Towne, W. D., Rahimtoola, S. H., Sinno, M. Z., Loeb, H. S., Rosen, K. M., Gunnar, R. M. ibid. 1975, 51, 988. 7. Criley, J. M., Lewis, K. B., Humphries, J. O., Ross, R. S. Br. Heart J. 1966, 28, 488. 8. Aranda, J. M., Befeler, B., El-Sherif, N., Castellanos, A., Lazzara, R. Am. J. Med. 1976, 60, 997. 9. Kerber, R. E., Isaeff, D. I., Hancock, E. W. New Engl. J. Med. 1971, 284, 691.
Popp, R. L., Brown, O. R., Silvermann, J. F., Harrison, D. C. Circulation, 1974, 49, 428. 11. Demaria, A. N., King, J. F., Bogren, H. G., Lies, J. E., Mason, D. T. ibid. 1974, 50, 33. 12. Procacci, P. M., Savran, V., Schrieiter, S. L., Bryson, A. L. New Engl. J. Med. 1976, 294, 1086. 13. Iskandrian, A. S., Kotler, M. N., Kimbiris, D., Levites, R., Bemis, C. E., Minzz, G., Forman, H. Cardiology, 1978, 63, 321. 10.
139
auscultation and on echocardiography,14 but with echocardiography false-positive diagnoses are easily made.15 16 SMITH and others 17 saw bulging of the posterior leaflet of the mitral valve, in the absence of a click or murmur, in 43% of 366 consecutive angiograms and they suggest that if there are no other features of the syndrome such a common finding should not be designated abnormal. Clearly considerable caution must be observed before floppy mitral valve3is diagnosed. The aetiology of the syndrome is diverse. There is certainly a familial incidence’g with a probable dominant inheritancels (it has been reported in twin physicians19). It may be found as an integral part of generalised connective-tissue disorders such as Marfan’s syndrome,18 20 osteogenesis imperfecta,21 and the Ehlers-Danlos syndrome.22 Degeneration of the connective tissue of the mitralvalve apparatus may explain the rising prevalence with age. 13 Other conditions associated with the floppy mitral valve are rheumatic carditis 18 and atrial septal defect .24 There has also been considerable controversy over the cause of the damage. Myxomatous degeneration has been seen in the mitral-valve leaflets and the chordae tendineae, 21 26 but this is non-specific and possibly related to age,23 with a decreased collagen content leading to valve prolapse and chordal rupture. Disruption of the collagenous tissue may also explain the association with the connective-tissue disorders. DAVIES and others23 suggest that the essential pathological process is a weakening of the central collagenous core of the valve apparatus which allows the cusps on
to expand.23 This, they believe, is partly age-related and partly genetically determined; it happens to the other heart valves as well. In their survey of 1984 routine hospital necropsies this group found prolapse of the valve in about 5% (rising with age), and in more than three-quarters of these, murmurs had been recorded. In all but 1 of the 23 patients with severe disruption of the valve, loud pansystolic murmurs had been heard, and in a third of these patients mitral incompetence had been the cause of death.
14. Markiewitz, W., Stoner,
J., London, E., Hunt, A., Popp, R. L. Circulation, 1976, 53, 464. 15. Weiss, A. N., Mimbs, J. W., Ludbrook, P. A., Sobel, B. E. ibid. 1975, 52, 1091. 16. Sahn, D. J., Wood, J.,
INTRACRANIAL PRESSURE IN CHILDHOOD CONVULSIONS ONE in fifteen children has an epileptic fit during the first seven years of life: one in two hundred adults has epilepsy. This spontaneous reduction in the proclivity to epileptic fits has led many to discount convulsions occurring in the early years of childhood. Now we recognise that such an expectant policy is no longer justifiedthat convulsions can themselves result in cerebral damage.1Minns and Brown3 have had the opportunity to investigate the pathogenesis of convulsion-induced cerebral damage. During the monitoring of intracranial pressure in various cerebral disorders, five children had convulsions, and the effect of a convulsion was to raise intracranial pressure. A normal pre-ictal pressure of < 10 mm Hg could rise to 30-40 mm Hg and the increased pressure could persist for up to 20 minutes after a single major convulsion. Minns and Brown relate their observations on intracranial-pressure changes to another known effect of epileptic convulsions-namely, the accompanying autonomic sympathetic discharge.4 This discharge results in a rise of blood-pressure, tachycardia, and increased cerebral blood-flow, an adaptation likely to meet the increased oxygen demands of the excited discharging neurons. This increased cerebral 27. Massie,
Allen, H. D., Peoples, W., Goldberg, S. J. Am. J. Cardiol. 1977, 39, 422. 17. Smith, E. R., Fraser, D. B., Purdy, J. W., Anderson, R. N. ibid. 1977, 40,
165. 18. Pocock, W. A., Barlow, J. B. Am. J. Med. 1971, 51, 731. 19. Girard, D. E., Girard, J. B. Am. Heart.J. 1977, 94, 813. 20. Brown, O. R., Demots, H., Kloster, F. E., Roberts, A., Menashe, V. D., Beals, R. K. Circulation, 1975, 52, 651. 21. Wood, S. J., Thomas, J., Braimbndge, M. V. Br. Heart J. 1973, 35, 103. 22. Brandt, K. D., Sumner, R. D., Ryan, T. J., Cohen, A. S. Am. J. Cardiol.
1975, 36, 524. 23. Davies, M. J., Moore, B. P., Braimbridge, M. V. Br. Heart J. 1978, 40, 468. 24. Betrui, A., Wigle, E. D., Felderhof, C. H., McLoughlin, M. J. Am. J. Car-
diol. 1975, 35, 363. 25. Bittar, N., Sosa, J. A. Circulation, 1968, 26. Kern, W. H., Tucker, B. L. Am. Heart J.
If a floppy mitral valve is diagnosed, what then? There do seem to be some circumstances in which the abnormality is important. It has been blamed, in the absence of any other abnormality, for atypical and bizarre chest pains. 5 27 The electrocardiogram may be abnormal, with T-wave inversion5 and arrhythmias,28-30 and these arrhythmias seem to be responsible for some sudden deaths in young people.31 The floppy mitral valve is indeed one factor in the aetiology of sudden death at all ages: DAVIES and others found 13 such instances in five years of forensic necropsies.23 Bacterial endocarditis may start on the atrial surface of the cusp.32 In general, however, the floppy mitral valve carries only a very slight risk of complications, and patients with an isolated systolic click or murmur are best told they are normal. There is perhaps one exception. Pilots, both commercial and military, may be subject to sudden acceleration which, by causing prolapse, could render the valve seriously and suddenly incompetent. 33
38, 763. 1972, 84, 294.
B., Botvimck, E. H., Shames, D., Taradash, M., Werner, J., Schiller, N. Circulation, 1978, 57, 19. 28. Sloman, G., Wong, M., Walker, J. Am. Heart J. 1972, 83, 312. 29. Josephson, M. E., Horowitz, L. N., Kastor, J. A. Circulation, 1978, 57, 111. 30. Gooch, A. S., Vicencio, F., Maranhao, V., Goldberg, H. Am. J. Cardiol. 1972, 29, 611. 31. Jeresaty, R. M. ibid. 1976, 37, 317. 32. Lachman, A. S., Bramwell-Jones, D. M., Lakier, J. B., Pocock, W. A., Barlow, J. B. Br. Heart J. 1975, 37, 326. 33 Towne, W. D., Rahimtoola, S. H., Rosen, K. M., Casten, C. T., Gummar, R. M. Aerospace Med. 1971, 42, 341. 1. Aicardi, J., Baraton, J. Devl Med. Chld Neurol. 1971, 13, 660. 2. Gastaut, H., Poirier, F., Payan, H., Salamon, G., Toga, M., Vigouroux, M. Epilepsia, Amsterdam, 1960, 1, 418. 3. Minns, R. A., Brown, J. K. Devl Med. ChldNeurol. 1978, 20, 561. 4. Meldrum, B. S. in A Textbook of Epilepsy (edited by J. Laidlaw and A. Richens); p. 334. Edinburgh, 1976.
home visits as against 2-4 in those without (P=0’03 and 0-004, respectively). Whilst this is not as rewarding a result as one might have hoped for, it is no cause for abandoning the concept, and at the end of the trial 90% of those recording their own B.P. regarded the method as useful. No-one has studied the benefits to patients, employers, and doctors in time or money. In view of the numbers, these are likely to be substantial to all parties. FINNERTY and othersl2 in one hypertension clinic found that the time spent waiting and the lack of personal relationship with the doctor were two potent reasons for defaulting. Visits to the doctor will still, of course, be necessary; and if fewer, there might be time to make them more personal. Once in a while, the aneroid sphygmomanometer should be checked against a mercury column; extra time will have to be spent also in explaining how to use the equipment, and under the N.H.S. there is the knotty problem of who is to pay for it. So long as self-recording does not worry and upset the patient or his family, the sense of responsibility engendered seems a worthwhile end in itself. This would not be the first instance of patients being entrusted with their own treatment, with medical back-up. This sort of doctor/patient relationship has existed for many years in the management of diabetes, where self-care is now being further developed with machines for measuring blood-sugar at home-a technique which seems to be popular with patients14 15 and a great help to their doctors. With blood-pressure we need to know more about the long-term results with self-recording, and, just because we are failing so often to lower patients’ B.P. adequately and commerce is hot on the trail, there is no justification for a sudden rush into this activity. Tradition inhibits doctors from crediting laymen with the ability to look after themselves. But there are strong arguments for putting the hypertensive ball into the patient’s court.
The
Floppy Mitral Valve
How are whoops, honks, clicks, and other systolic sounds connected? The answer is in the prolapsing-mitral-valve syndrome, which occurs when the mitral-valve leaflets balloon or prolapse into the left atrium during systole. The many names given to this syndrome-the floppy mitral valve, the ballooning mitral valve, the redundant-cusp syndrome, the systolic click-murmur syndrome, and so onl-reflect a shortage of agreement on what exactly the syndrome is. Until the early 1960s, sys13. Johnson, A. L., Taylor, D. W., Sackett, D. L., Dunnett, C. W., Shimizu, A. G. Can med. Ass. J. 1978, 119, 1034. 14. Sönksen, P. H., Judd, S. L., Lowy, C. Lancet, 1978, i,729. 15. Walford, S., Gale, E. A. M., Allison, S. P., Tattersall, R. B. ibid. p. 732. 1 Abrams, J. Am. Heart. J. 1976, 92, 413.
tolic clicks
were regarded as extracardiac. Then REID2 challenged this view; and subsequently BARLOW3 and others4 showed that both clicks and the "innocent" late systolic murmur heard at the apex can originate from the mitral valve. Thus the concept of the "mitral valve click-murmur syndrome" developed. Certain manoeuvres that diminish ventricular volume, such as amyl-nitrite inhalation, upright posture, and the strain phase of the Valsalva manoeuvre, may reduce the intensity of the murmur and move the click nearer the first heart-sound; whereas the reverse may occur with increased ventricular volume, for example with phenylephrine, squatting, and the release phase of the Valsalva manaeuvre.5 At the bedside, systolic sounds can sometimes be elucidated by listening with the patient in turn sitting, standing, and squatting.5 Alteration in heart-rate may cause the murmur and click to disappear altogether.6 These clicks and murmurs, angiography reveals, coincide with the point of maximal prolapse of the mitral valve into the left atrium.7 The mitral-valve abnormality varies from prolapse of single leaflets and lengthening of the chordae tendinese to gross mitral incompetence with ballooning of both leaflets. Clicks seem to occur in the milder abnormalities ; with slightly more severe disruption a late systolic murmur is heard; and with haemodynamically important mitral regurgitation the murmur is pansystolic.8 Real-time echocardiography clarifies matters further,9 10 three distinctive patterns being recognised-midsystolic buckling of one or both mitral-valve leaflets; pansystolic bowing; and pansystolic collapse. Pansystolic bowing is the most
frequent. 11I How
common
are
these
auscultatory, angio-
and echocardiographic findings? Systolic clicks or late systolic murmurs were found in 74 (6.3%) of 1169 healthy young females, of whom 60 also had positive echocardiographic findings. 12 Much the same incidence of mitral-valve prolapse was found in patients having routine angiography, this abnormality being unsuspected in just under half.13 Higher incidences have been reported, both
graphic,
2. 3.
Reid, J. V.O.S.Afr. med. J. 1961, 35, 353. Barlow, J. B., Bosman, C. K., Pocock, W. A., Marchand, P. Br. Heart J. 1968, 30, 203. 4. Hancock, E. W., Cohn, K. Am. J. Med. 1966, 41, 183. 5. Devereux, R. B., Perloff, J. K., Reichek, N., Josephson, M. E. Circulation, 1976, 54, 3. 6. Towne, W. D., Rahimtoola, S. H., Sinno, M. Z., Loeb, H. S., Rosen, K. M., Gunnar, R. M. ibid. 1975, 51, 988. 7. Criley, J. M., Lewis, K. B., Humphries, J. O., Ross, R. S. Br. Heart J. 1966, 28, 488. 8. Aranda, J. M., Befeler, B., El-Sherif, N., Castellanos, A., Lazzara, R. Am. J. Med. 1976, 60, 997. 9. Kerber, R. E., Isaeff, D. I., Hancock, E. W. New Engl. J. Med. 1971, 284, 691.
Popp, R. L., Brown, O. R., Silvermann, J. F., Harrison, D. C. Circulation, 1974, 49, 428. 11. Demaria, A. N., King, J. F., Bogren, H. G., Lies, J. E., Mason, D. T. ibid. 1974, 50, 33. 12. Procacci, P. M., Savran, V., Schrieiter, S. L., Bryson, A. L. New Engl. J. Med. 1976, 294, 1086. 13. Iskandrian, A. S., Kotler, M. N., Kimbiris, D., Levites, R., Bemis, C. E., Minzz, G., Forman, H. Cardiology, 1978, 63, 321. 10.
139
auscultation and on echocardiography,14 but with echocardiography false-positive diagnoses are easily made.15 16 SMITH and others 17 saw bulging of the posterior leaflet of the mitral valve, in the absence of a click or murmur, in 43% of 366 consecutive angiograms and they suggest that if there are no other features of the syndrome such a common finding should not be designated abnormal. Clearly considerable caution must be observed before floppy mitral valve3is diagnosed. The aetiology of the syndrome is diverse. There is certainly a familial incidence’g with a probable dominant inheritancels (it has been reported in twin physicians19). It may be found as an integral part of generalised connective-tissue disorders such as Marfan’s syndrome,18 20 osteogenesis imperfecta,21 and the Ehlers-Danlos syndrome.22 Degeneration of the connective tissue of the mitralvalve apparatus may explain the rising prevalence with age. 13 Other conditions associated with the floppy mitral valve are rheumatic carditis 18 and atrial septal defect .24 There has also been considerable controversy over the cause of the damage. Myxomatous degeneration has been seen in the mitral-valve leaflets and the chordae tendineae, 21 26 but this is non-specific and possibly related to age,23 with a decreased collagen content leading to valve prolapse and chordal rupture. Disruption of the collagenous tissue may also explain the association with the connective-tissue disorders. DAVIES and others23 suggest that the essential pathological process is a weakening of the central collagenous core of the valve apparatus which allows the cusps on
to expand.23 This, they believe, is partly age-related and partly genetically determined; it happens to the other heart valves as well. In their survey of 1984 routine hospital necropsies this group found prolapse of the valve in about 5% (rising with age), and in more than three-quarters of these, murmurs had been recorded. In all but 1 of the 23 patients with severe disruption of the valve, loud pansystolic murmurs had been heard, and in a third of these patients mitral incompetence had been the cause of death.
14. Markiewitz, W., Stoner,
J., London, E., Hunt, A., Popp, R. L. Circulation, 1976, 53, 464. 15. Weiss, A. N., Mimbs, J. W., Ludbrook, P. A., Sobel, B. E. ibid. 1975, 52, 1091. 16. Sahn, D. J., Wood, J.,
INTRACRANIAL PRESSURE IN CHILDHOOD CONVULSIONS ONE in fifteen children has an epileptic fit during the first seven years of life: one in two hundred adults has epilepsy. This spontaneous reduction in the proclivity to epileptic fits has led many to discount convulsions occurring in the early years of childhood. Now we recognise that such an expectant policy is no longer justifiedthat convulsions can themselves result in cerebral damage.1Minns and Brown3 have had the opportunity to investigate the pathogenesis of convulsion-induced cerebral damage. During the monitoring of intracranial pressure in various cerebral disorders, five children had convulsions, and the effect of a convulsion was to raise intracranial pressure. A normal pre-ictal pressure of < 10 mm Hg could rise to 30-40 mm Hg and the increased pressure could persist for up to 20 minutes after a single major convulsion. Minns and Brown relate their observations on intracranial-pressure changes to another known effect of epileptic convulsions-namely, the accompanying autonomic sympathetic discharge.4 This discharge results in a rise of blood-pressure, tachycardia, and increased cerebral blood-flow, an adaptation likely to meet the increased oxygen demands of the excited discharging neurons. This increased cerebral 27. Massie,
Allen, H. D., Peoples, W., Goldberg, S. J. Am. J. Cardiol. 1977, 39, 422. 17. Smith, E. R., Fraser, D. B., Purdy, J. W., Anderson, R. N. ibid. 1977, 40,
165. 18. Pocock, W. A., Barlow, J. B. Am. J. Med. 1971, 51, 731. 19. Girard, D. E., Girard, J. B. Am. Heart.J. 1977, 94, 813. 20. Brown, O. R., Demots, H., Kloster, F. E., Roberts, A., Menashe, V. D., Beals, R. K. Circulation, 1975, 52, 651. 21. Wood, S. J., Thomas, J., Braimbndge, M. V. Br. Heart J. 1973, 35, 103. 22. Brandt, K. D., Sumner, R. D., Ryan, T. J., Cohen, A. S. Am. J. Cardiol.
1975, 36, 524. 23. Davies, M. J., Moore, B. P., Braimbridge, M. V. Br. Heart J. 1978, 40, 468. 24. Betrui, A., Wigle, E. D., Felderhof, C. H., McLoughlin, M. J. Am. J. Car-
diol. 1975, 35, 363. 25. Bittar, N., Sosa, J. A. Circulation, 1968, 26. Kern, W. H., Tucker, B. L. Am. Heart J.
If a floppy mitral valve is diagnosed, what then? There do seem to be some circumstances in which the abnormality is important. It has been blamed, in the absence of any other abnormality, for atypical and bizarre chest pains. 5 27 The electrocardiogram may be abnormal, with T-wave inversion5 and arrhythmias,28-30 and these arrhythmias seem to be responsible for some sudden deaths in young people.31 The floppy mitral valve is indeed one factor in the aetiology of sudden death at all ages: DAVIES and others found 13 such instances in five years of forensic necropsies.23 Bacterial endocarditis may start on the atrial surface of the cusp.32 In general, however, the floppy mitral valve carries only a very slight risk of complications, and patients with an isolated systolic click or murmur are best told they are normal. There is perhaps one exception. Pilots, both commercial and military, may be subject to sudden acceleration which, by causing prolapse, could render the valve seriously and suddenly incompetent. 33
38, 763. 1972, 84, 294.
B., Botvimck, E. H., Shames, D., Taradash, M., Werner, J., Schiller, N. Circulation, 1978, 57, 19. 28. Sloman, G., Wong, M., Walker, J. Am. Heart J. 1972, 83, 312. 29. Josephson, M. E., Horowitz, L. N., Kastor, J. A. Circulation, 1978, 57, 111. 30. Gooch, A. S., Vicencio, F., Maranhao, V., Goldberg, H. Am. J. Cardiol. 1972, 29, 611. 31. Jeresaty, R. M. ibid. 1976, 37, 317. 32. Lachman, A. S., Bramwell-Jones, D. M., Lakier, J. B., Pocock, W. A., Barlow, J. B. Br. Heart J. 1975, 37, 326. 33 Towne, W. D., Rahimtoola, S. H., Rosen, K. M., Casten, C. T., Gummar, R. M. Aerospace Med. 1971, 42, 341. 1. Aicardi, J., Baraton, J. Devl Med. Chld Neurol. 1971, 13, 660. 2. Gastaut, H., Poirier, F., Payan, H., Salamon, G., Toga, M., Vigouroux, M. Epilepsia, Amsterdam, 1960, 1, 418. 3. Minns, R. A., Brown, J. K. Devl Med. ChldNeurol. 1978, 20, 561. 4. Meldrum, B. S. in A Textbook of Epilepsy (edited by J. Laidlaw and A. Richens); p. 334. Edinburgh, 1976.